{
  "abstract": "Incretin-based pharmacotherapies produce substantial weight loss, but their comparative effects on lean tissue remain incompletely characterized. We systematically reviewed randomized controlled trials in adults with overweight, obesity, and/or type 2 diabetes. The prospectively registered primary outcome was the between-group difference in relative percentage change from baseline in total lean body mass measured by dual-energy X-ray absorptiometry (DXA) at 48 to <80 weeks; absolute DXA change in kilograms was the key secondary outcome. The auditable record-level dataset comprised 6,526 imported records from PubMed and ClinicalTrials.gov; after the removal of 250 within-PubMed duplicates, 6,276 records were screened, and 52 trial families met review-level eligibility. Three direct contrasts had defensible precision for the registered primary outcome: pooled tirzepatide versus placebo, -8.3 percentage points (95% confidence interval {CI}: -10.6 to -6.1); semaglutide 1.0 mg versus placebo, -3.81 (-6.57 to -1.06); and semaglutide 2.4 mg versus placebo, -6.06 (-8.79 to -3.33). Because the two BELIEVE semaglutide contrasts shared a placebo group and their joint covariance was unavailable, they were not treated as independent edges in a single dose-specific network meta-analysis (NMA). Separate placebo-anchored sensitivity comparisons of pooled tirzepatide versus semaglutide were -4.49 percentage points (95% CI: -8.05 to -0.93) for semaglutide 1.0 mg and -2.24 (-5.78 to 1.30) for semaglutide 2.4 mg; both were graded very low confidence. For the key secondary absolute DXA outcome, mean differences versus placebo were -3.43 kg (95% CI: -4.74 to -2.13) for semaglutide 2.4 mg, -4.40 kg (-5.60 to -3.20) for pooled tirzepatide, and -5.90 kg (-7.28 to -4.52) for mazdutide 9 mg. DXA-derived lean mass is not synonymous with skeletal-muscle mass or function, and these reductions should not by themselves be interpreted as evidence of sarcopenia or clinically harmful muscle loss. Randomized evidence therefore supports measurable lean-mass loss during incretin-associated weight reduction, but sparse network geometry, heterogeneous estimands, selected body-composition substudies, and incomplete reporting preclude a reliable comparative treatment ranking.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Family Medicine, Prince Sultan Military Medical City, Riyadh, SAU",
    "Department of Family Medicine, Royal Guard Medical Services, Riyadh, SAU",
    "College of Medicine, Ibn Sina National College for Medical Studies, Jeddah, SAU"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zahi M Alhamad"
    },
    {
      "affs": [
        0
      ],
      "name": "Naif AlShalhoub"
    },
    {
      "affs": [
        1
      ],
      "name": "Abdulrahman Al-mana"
    },
    {
      "affs": [
        0
      ],
      "name": "Faisal E Almutairi"
    },
    {
      "affs": [
        2
      ],
      "name": "Hamad M Alshalhoub"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dzcczbgrb40ds.bib",
  "cited_by": 0,
  "doi": "10.7759/cureus.117738",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13747210/",
  "id": "dzcczbgrb40ds",
  "issns": [
    "2168-8184"
  ],
  "landing_url": "https://doi.org/10.7759/cureus.117738",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Endocrinology/Diabetes/Metabolism"
    ],
    [
      "heading",
      "Nutrition"
    ],
    [
      "heading",
      "Therapeutics"
    ],
    [
      "openalex",
      "2712|Diabetes Treatment and Management"
    ]
  ],
  "openalex": "W7221345088",
  "pdf_url": "https://www.cureus.com/articles/533361-effects-of-incretin-based-pharmacotherapies-on-lean-body-mass-in-adults-with-overweight-obesity-or-type-2-diabetes-a-systematic-review-with-prespecified-network-meta-analysis-feasibility-assessment.pdf",
  "pmcid": "PMC13747210",
  "pmid": "43005990",
  "published": "2026-10-10",
  "publisher": "Cureus Inc.",
  "ris": "https://research.draconitic.com/paper/dzcczbgrb40ds.ris",
  "sources": [
    {
      "first_seen": "2026-11-11T12:24:21Z",
      "native_id": "PMC13747210",
      "source": "pmc",
      "url": "https://doi.org/10.7759/cureus.117738"
    },
    {
      "first_seen": "2026-11-12T15:22:43Z",
      "native_id": "MED:43005990",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/43005990"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "heading:Nutrition",
      "subfield": "nutrition"
    }
  ],
  "title": "Effects of Incretin-Based Pharmacotherapies on Lean Body Mass in Adults With Overweight, Obesity, or Type 2 Diabetes: A Systematic Review With Prespecified Network Meta-Analysis Feasibility Assessment",
  "title_text": "Effects of Incretin-Based Pharmacotherapies on Lean Body Mass in Adults With Overweight, Obesity, or Type 2 Diabetes: A Systematic Review With Prespecified Network Meta-Analysis Feasibility Assessment",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T03:20:44Z",
  "url": "https://research.draconitic.com/paper/dzcczbgrb40ds",
  "venue": "Cureus",
  "versions": []
}